Δ160p53 enhances tumorigenicity

Lina Miyawaki et al.

Wild-type p53is a tumor suppressor gene that responds to various kinds of damage by inducing cell cycle arrest or apoptosis. When mutated,p53 starts to possess oncogenic potential facilitating tissues to form tumors. It has recently been reported by our group that mutant p53activity depends on the expression of p53isoforms. Expression of p53 isoforms is controlled by alternative promoters, alternative splice sites, and alternative initiation codons. There are three shorter p53isoforms that result from alternative initiation of translation. We have previously shown that some of the most common p53cancer mutants express a larger number and higher levels of shorter p53 protein isoforms that are translated from the mutatedFLp53 (full length p53) mRNA. Cells expressing mutant p53exhibit “gain-of-function”cancer phenotypes, such as enhanced cell survival, proliferation, invasion and adhesion, altered mammary tissue architecture and invasive cell structures (Candeiaset al., 2016). To investigate the function of the Δ160p53 isoform, three independent experiments were conducted using stable A549 cell lines with integrated empty vector (pcDNA3.1) or Δ160p53-expressing vector. Experiments show that cells expressing Δ160p53 can make more colonies than cells expressing endogenous p53only, which means p53isoform provides another mutant gain-of-function type of activity to cancer cells.